Kochem Matthew, Breslin Paul A S
Rutgers University Department of Nutritional Sciences, New Brunswick, NJ, United States of America.
Monell Chemical Senses Center Philadelphia, PA, United States of America.
PLoS One. 2017 Mar 1;12(3):e0172534. doi: 10.1371/journal.pone.0172534. eCollection 2017.
In humans, umami taste can increase the palatability of foods rich in the amino acids glutamate and aspartate and the 5'-ribonucleotides IMP and GMP. Umami taste is transduced, in part, by T1R1-T1R3, a heteromeric G-protein coupled receptor. Umami perception is inhibited by sodium lactisole, which binds to the T1R3 subunit in vitro. Lactisole is structurally similar to the fibrate drugs. Clofibric acid, a lipid lowering drug, also binds the T1R3 subunit in vitro. The purpose of this study was to determine whether clofibric acid inhibits the umami taste of glutamate in human subjects. Ten participants rated the umami taste intensity elicited by 20 mM monosodium glutamate (MSG) mixed with varying concentrations of clofibric acid (0 to 16 mM). In addition, fourteen participants rated the effect of 1.4 mM clofibric acid on umami enhancement by 5' ribonucleotides. Participants were instructed to rate perceived intensity using a general Labeled Magnitude Scale (gLMS). Each participant was tested in triplicate. Clofibric acid inhibited umami taste intensity from 20 mM MSG in a dose dependent manner. Whereas MSG neat elicited "moderate" umami taste intensity, the addition of 16 mM clofibric acid elicited only "weak" umami intensity on average, and in some subjects no umami taste was elicited. We further show that 1.4 mM clofibric acid suppressed umami enhancement from GMP, but not from IMP. This study provides in vivo evidence that clofibric acid inhibits glutamate taste perception, presumably via T1R1-T1R3 inhibition, and lends further evidence that the T1R1-T1R3 receptor is the principal umami receptor in humans. T1R receptors are expressed extra-orally throughout the alimentary tract and in regulatory organs and are known to influence glucose and lipid metabolism. Whether clofibric acid as a lipid-lowering drug affects human metabolism, in part, through T1R inhibition warrants further examination.
在人类中，鲜味能增加富含氨基酸谷氨酸和天冬氨酸以及5'-核糖核苷酸肌苷酸（IMP）和鸟苷酸（GMP）的食物的适口性。鲜味部分通过异源三聚体G蛋白偶联受体T1R1-T1R3进行转导。在体外，乳酰异硫氰酸酯与T1R3亚基结合，从而抑制鲜味感知。乳酰异硫氰酸酯在结构上与贝特类药物相似。降脂药物氯贝酸在体外也能与T1R3亚基结合。本研究的目的是确定氯贝酸是否会抑制人类受试者对谷氨酸的鲜味感受。10名参与者对20 mM谷氨酸钠（MSG）与不同浓度氯贝酸（0至16 mM）混合所引发的鲜味强度进行评分。此外，14名参与者对1.4 mM氯贝酸对5'-核糖核苷酸增强鲜味的作用进行评分。参与者被要求使用通用标记量值量表（gLMS）对感知强度进行评分。每位参与者均进行三次测试。氯贝酸以剂量依赖的方式抑制20 mM MSG的鲜味强度。纯MSG引发“中等”鲜味强度，而添加16 mM氯贝酸平均仅引发“微弱”鲜味强度，在一些受试者中未引发鲜味。我们进一步表明，1.4 mM氯贝酸抑制了GMP增强的鲜味，但未抑制IMP增强的鲜味。本研究提供了体内证据，表明氯贝酸可能通过抑制T1R1-T1R3来抑制谷氨酸味觉感知，并进一步证明T1R1-T1R3受体是人类主要的鲜味受体。T1R受体在整个消化道的口外以及调节器官中表达，并且已知会影响葡萄糖和脂质代谢。氯贝酸作为一种降脂药物是否部分通过抑制T1R来影响人类代谢，值得进一步研究。
